The focus of this proposal is to study the role of GABAergic inhibition in sharpening orientation tuning in the primary visual cortex (V1). Pharmacological techniques will be used to block inputs from the GABAergic inhibitory interneurons, which may have a central role in activity-dependent cortical plasticity. The effects of such blockade near pinwheel centers and in the orientation domains will be assessed to test the hypothesis that sharp orientation tuning of neurons near pinwheel centers, compared to that in orientation domains, is more sensitive to changes in the balance of inhibition and excitation. Specifically, focal iontophoresis of bicuculline, a GABA receptor antagonist, will be applied to block inhibitory action of GABA receptors and thus reduce or remove inhibition. The functional consequences of such blockade of inhibition will be investigated by single unit recording and/or intrinsic signal optical imaging experiments. An alternative approach is to inactivate interneurons by in vivo viral-based RNA interference (RNAi) on genes specifically expressed in GABAergic neurons and critical to the neuronal function, e.g. glutamate decarboxylase 67. The effects of RNAi will be assessed by physiological studies using optical imaging and recording techniques. [unreadable] [unreadable] [unreadable]